Tobacco use and obesity are the top preventable causes of death in the United States. Behavioral studies show that obese smokers may be less sensitive to nicotine reward compared to healthy weight smokers. Neuroimaging studies demonstrate that smokers are hyper-responsive to smoking cues and obese groups are hyper-responsive to food cues. There is significant overlap between the brain regions involved in reward processing and behavioral control. These findings have added support to shared neural network models of smoking, overeating, and other behaviors requiring regulation of impulses. However, little is known about how these reward areas of the brain respond to food and smoking images when an individual is both a smoker and obese. The long term goal of this research is to increase our understanding of how the neural systems of reward differentially respond in the case of co-morbid obesity and nicotine addiction, which will inform smoking cessation and weight management treatment programs designed for the specific needs of obese smokers. The proposed research project will employ functional magnetic resonance imaging (fMRI) to examine the neural systems of reward while obese and healthy weight smokers view food and smoking images in the scanner. We hypothesize that obese smokers will show increased responses to food cues and decreased responses to smoking cues compared to healthy weight smokers. We will scan healthy weight smokers and obese smokers while they view smoking cues and food cues. The project will address the following Specific Aims: 1. Characterize brain systems underlying cue processing of a preferred substance (food or smoking images) in a combined group of smokers (regardless of weight). 2. Identify brain responses associated with co-morbid obesity and nicotine addiction by examining fMRI activation differences between groups of healthy weight and obese smokers. PUBLIC HEALTH RELEVANCE: Results of this work are highly significant to public health and could lead to a better understanding of how co- morbidities of obesity and nicotine addiction relate to brain activations in response to food and smoking images. Findings from this study will have significant implications for understanding mechanisms of obesity and nicotine addiction, and the effects of co-morbidities on brain function in obese and healthy weight smokers. Findings may eventually lead to more effective interventions.